Liver damage by infiltrating CD8(+) T cells is Fas dependent

Ag stimulation of CD8(+) lymphocytes in vivo results in their migration to various tissues as well as the activation of a cytolytic program involving perforin, TNF-alpha, and Fas ligand. The liver is one of the main sites for infiltration by activated CD8(+) T cells, and this is followed by the deat h of hepatocytes. The contribution of the various cytolytic components to t his process is unclear. Hepatocyte damage by CD8(+) T cells was studied usi ng the MHC class I-restricted OVA-specific TCR transgenic mouse (OT-1) to e xamine the contribution of Fas to hepatocyte death. Activated CD8(+) T cell s from both OT-1 and Fas-deficient OT-1/pr mice migrated to the liver in si milar numbers after OVA administration, but only in OT-1 mice was there evi dence of significant hepatocyte damage histologically and by elevation of s erum aspartate transaminase. These differences were not the result of ineff icient induction of cytolytic activity in OT-1/pr liver T cells, since they were as cytolytic in vitro as OT-1 liver T cells. This was supported by fi ndings of similar high levels of message for perforin, TNF-alpha, and Fas l igand in liver lymphocytes from both mice. These findings demonstrate that following Ag activation, infiltrating liver CD8(+) T lymphocytes induce hep atocyte damage in a Fas-dependent manner.